A Prospective, Open-label, Single-arm Multicenter Clinical Study of Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Untreated Follicular Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Objective response rate，ORR
研究概览
简要总结
This study is planned to prospectively evaluates the efficacy and safety of the zanubrutinib, obinutuzumab, and lenalidomide (ZGR) combination regimen in treatment-naïve follicular lymphoma (FL) patients in a Chinese population.
详细描述
Regarding chemotherapy-free first-line treatment regimens, current targeted therapies primarily focus on lenalidomide combined with anti-CD20 antibodies. Chemotherapy-free regimens such as rituximab plus lenalidomide (R²) or obinutuzumab plus lenalidomide (O-Len) have been recommended for clinical use. Encouraged by the promising efficacy of dual-targeted therapies, the potential of triple-combination therapy-comprising a BTK inhibitor (BTKi), an anti-CD20 monoclonal antibody, and lenalidomide-has garnered increasing attention in untreated hematologic malignancies. Most existing studies have concentrated on BTKi combined with rituximab and lenalidomide (e.g., ibrutinib + R²).
Given current clinical needs and available evidence, this study aims to explore a novel chemotherapy-free triple regimen: zanubrutinib combined with obinutuzumab and lenalidomide (ZGR) in treatment-naïve follicular lymphoma (FL) patients. This combination is expected to provide a new treatment paradigm for untreated FL, offering high antitumor efficacy while minimizing toxicity, thereby improving patients' quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gender: No restrictions; age ≥18 years.
- •Diagnosis: Histologically confirmed CD20-positive follicular lymphoma (FL), Grade 1, 2, or 3A, per 2016 WHO classification. All patients must provide sufficient archived or fresh tumor tissue samples for immunohistochemical (IHC) analysis.
- •Disease Stage & Treatment Need:
- •Stage III or IV disease, or Stage II with bulky disease, meeting at least one of the following criteria:
- •a) Bulky disease: Lymph node or extranodal (excluding spleen) mass with maximum diameter ≥7 cm.
- •b) Local symptoms or organ dysfunction due to progressive lymphadenopathy or extranodal tumor mass.
- •c) B symptoms (fever, night sweats, or unintentional weight loss >10% of body weight within ≤6 months).
- •d) Symptomatic extranodal involvement (e.g., pleural/peritoneal effusion).
- •e) Cytopenias due to bone marrow infiltration (hemoglobin <10 g/dL, absolute neutrophil count [ANC] <1.0×10⁹/L, platelets <100×10⁹/L).
- •f) Involvement of ≥3 lymph nodes, each ≥3 cm in diameter.
- •g) Symptomatic splenomegaly.
- •Prior Therapy: No prior systemic therapy for FL.
- •ECOG Performance Status: ≤
- •Measurable Disease: At least one measurable lesion (>2 cm in longest diameter by CT/MRI).
- •Life Expectancy: ≥6 months.
- •Adequate Organ Function:
- •a) ANC ≥1.0×10⁹/L (without growth factor support).
- •b) Platelets ≥50×10⁹/L (untransfused within 7 days).
- •c) Total bilirubin (TBIL) ≤1.5×ULN.
- •d) ALT/AST ≤3×ULN.
- •e) Creatinine clearance ≥30 mL/min (calculated by modified Cockcroft-Gault formula).
- •Contraception: Men and women of childbearing potential must agree to use highly effective contraception during the study and for 4 weeks after treatment discontinuation.
- •Informed Consent: Patients must voluntarily participate and sign informed consent forms (ICF).
排除标准
- •Patients meeting any of the following criteria will be excluded from this study:
- •Histologic evidence of central nervous system (CNS) lymphoma, leptomeningeal lymphoma, or transformation to high-grade lymphoma (e.g., diffuse large B-cell lymphoma, DLBCL).
- •Grade 3B follicular lymphoma (FL) or transformed FL.
- •Ann Arbor Stage I FL.
- •Prior history of malignancy, unless the patient has been disease-free for ≥5 years and the treating physician deems the risk of recurrence low (exceptions: non-melanoma skin cancer, cured localized prostate cancer, carcinoma in situ of the cervix, or squamous intraepithelial lesions on PAP smear).
- •Use of any investigational drugs, antibiotics, or participation in another interventional clinical trial within 4 weeks prior to enrollment.
- •Major surgery (excluding lymph node biopsy) within 14 days before enrollment or anticipated need for major surgery during the study.
- •Prior treatment with zanubrutinib, obinutuzumab, or lenalidomide.
- •Immunodeficiency or autoimmune disease history, or chronic systemic steroid therapy (>10 mg/day prednisone equivalent) or immunosuppressive therapy within 7 days before enrollment.
- •Severe hepatic dysfunction (including severe jaundice, hepatic encephalopathy, refractory ascites, or hepatorenal syndrome), cachexia, or multi-organ failure with renal impairment.
- •Clinically significant cardiovascular abnormalities:
- •NYHA Class III/IV heart failure
- •Myocardial infarction within 6 months before enrollment, Malignant arrhythmias (including QTc ≥480 ms), Uncontrolled hypertension (Systolic blood pressure (SBP) ≥150 mmHg and diastolic blood pressure (DBP) ≥100 mmHg), Unstable angina.
- •Active infections:
- •HIV, active hepatitis B/C infection (HBV DNA ≥2000 IU/mL or HCV RNA detectable)
- •Uncontrolled systemic infections.
- •Bleeding disorders or coagulation abnormalities, or thrombotic events within 3 months.
- •Severe hypersensitivity to the active ingredients or excipients of the study drugs.
- •Pregnancy, lactation, or unwillingness to use effective contraception in women of childbearing potential.
- •Other conditions deemed unsuitable by the investigator.
研究组 & 干预措施
Experimental: Induction therapy of ZGR, and maintenance therapy of ZR
Induction therapy: All enrolled patients received the ZGR regimen (zanubrutinib, obinutuzumab, and lenalidomide) for Cycles 1-4. Tumor response was assessed after Cycle 4. Patients achieving complete response (CR) or partial response (PR) continued the same ZGR regimen for 2 additional cycles (Cycles 5-6).
Maintenance therapy: After completing induction therapy, patients with sustained CR/PR initiated maintenance therapy with zanubrutinib plus lenalidomide (ZR) for 18 months (1.5 years) or until disease progression, intolerable toxicity, or trial withdrawal (whichever occurred first)
干预措施: Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide (Drug)
Experimental: Induction therapy of ZGR, and maintenance therapy of ZR
Induction therapy: All enrolled patients received the ZGR regimen (zanubrutinib, obinutuzumab, and lenalidomide) for Cycles 1-4. Tumor response was assessed after Cycle 4. Patients achieving complete response (CR) or partial response (PR) continued the same ZGR regimen for 2 additional cycles (Cycles 5-6).
Maintenance therapy: After completing induction therapy, patients with sustained CR/PR initiated maintenance therapy with zanubrutinib plus lenalidomide (ZR) for 18 months (1.5 years) or until disease progression, intolerable toxicity, or trial withdrawal (whichever occurred first)
干预措施: Maintenance therapy: Zanubrutinib, lenalidomide (Drug)
结局指标
主要结局
Objective response rate，ORR
时间窗: up to the end of 6 cycles of treatment(each cycle is 28 days)]
Defined as the proportion of patients with complete or partial response as assessed by response to induction therapy
次要结局
- Best overall response rate (ORR) and complete response rate (CRR) during treatment(Up to the end of 6 cycles of treatment(each cycle is 28 days))
- Complete response rate，CRR(up to the end of 6 cycles of treatment(each cycle is 28 days))
- Progression-free survival (PFS)(up to 5 years)
- CRR and ORR at end of treatment(at the end of Cycle 24 (each cycle is 28 days))
- Duration of response (DOR)(up to 5 years)
- Time to response (TTR)(at the end of Cycle 24 (each cycle is 28 days))
- 2-year overall survival (OS) rate(up to 2 years)
- Proportion of patients with progression of disease within 24 months (POD24)(Up to the end of 2 years (each cycle is 28 days))
- The safety(up to 5 years)